ClinVar Miner

Submissions for variant NM_177924.5(ASAH1):c.536C>T (p.Thr179Ile) (rs766257867)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV000679928 SCV000807360 uncertain significance Spinal muscular atrophy-progressive myoclonic epilepsy syndrome 2017-09-01 criteria provided, single submitter clinical testing Likely pathogenicity based on finding it in trans with another missense mutation in a 14-year-old female with progressive cognitive impairment, flaccid proximal limb weakness with childhood onset, hyperreflexia, seizure disorder, dystonia, myoclonus, mild cerebral atrophy.
Medical Affairs, Dicerna Pharmaceuticals RCV000679928 SCV001161412 pathogenic Spinal muscular atrophy-progressive myoclonic epilepsy syndrome 2019-06-18 criteria provided, single submitter literature only It is our recommendation to update the status of variant c.536C>T from VUS to pathogenic due to recent publications discussing the pathogenicity of this variant. Multiple patients have been diagnosed with SMA-PME who carry the c.546C>T variant. In Sathe et al., 2014, DOI: 10.1016/j.ymgme.2013.12.226, the patient presented with SMA-PME according to Gene Reviews (https://www.ncbi.nlm.nih.gov/books/NBK488189/). Compound heterozygous variants, c.536C>T and c.125A>G, were identified in the patient using whole genome sequencing. Variant c.536C>T has been identified in an additional unrelated patients diagnosed with SMA-PME including a patient listed in Clinvar and identified at Baylor College of Medicine (SCV000807360.1) and 1 patient published in Cozma et al., 2017, DOI:10.1038/s41598-017-06604-2. Ceramide biomarker analysis in this patient (Cozma et al., 2017) along with 9 additional Farber disease patients and 2 SMA-PME patients demonstrated that C26:0 levels were significantly higher in Farber patients and SMA-PME patients compared to controls.

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